The purpose of this project is to provide a selection of infectious and pathogenic molecular clones of the highly pathogenic strain of HIV-2, HIV-2287. This will allow determination of the genetic factors that contribute to the rapid CD4+ cell depletion that is characteristically observed in infected macaques. Two macaques have been challenged; one with a pair of molecular clones that showed promising in vitro cytopathogenicity and the other with biological plasma isolates that demonstrated clonal characteristics in vitro. The biological isolates were equivalently infectious and pathogenic in vivo to the wild-type virus. The molecular clones, however, were minimally infectious. Further in vitro characterization is necessary. Both macaques have been euthanatized and full histopathology will be done on all tissues; selected lymphoid tissues will be examined for the presence of virus and additional characterization. FUNDING NIH grant RR00166.